Loenders B, Jorens P G, Herman A G
Division of Pharmacology, University of Antwerp (UIA), Wilrijk, Belgium.
Eur J Pharmacol. 1996 Jan 18;296(1):89-96. doi: 10.1016/0014-2999(95)00681-8.
By the simultaneous measurement of acetylcholine release and smooth muscle contraction in rabbit tracheal segments with and without epithelium, pre- as well as postsynaptic effects of this cell layer were studied on cholinergic neurotransmission. The epithelial cell layer exerted a presynaptic inhibitory influence on acetylcholine release, induced by KCl and electrical stimulation, with a concomitant decrease in the smooth muscle contractions. The responses elicited by exogenous acetylcholine, acting postsynaptically, were also inhibited in the presence of the epithelium. The epithelial effect was not accounted for by the production of inhibitory prostaglandins or a nitric oxide-synthase product. Furthermore, the epithelium did not function as a metabolic site for the degradation of acetylcholine. Phosphoramidon, an inhibitor of neutral endopeptidase, mimicked the effects of epithelium removal on the cholinergic responses to high frequency stimulation and on the acetylcholine-induced effects. Neutral endopeptidase inhibition did not further enhance the responses in epithelium-denuded segments. We therefore suggest that the inhibitory function of the epithelium can be partly explained by the activity of neutral endopeptidase, limiting the excitatory effects of tachykinins on cholinergic responses. An alteration in the neutral endopeptidase activity as a result of inflammatory responses and epithelial damage can contribute to the mechanism of airway hyperreactivity in asthma.
通过同时测量有上皮和无上皮的兔气管段中乙酰胆碱的释放和平滑肌收缩情况，研究了该细胞层对胆碱能神经传递的突触前和突触后效应。上皮细胞层对由氯化钾和电刺激诱导的乙酰胆碱释放产生突触前抑制作用，同时平滑肌收缩也随之减少。在外源性乙酰胆碱产生的突触后反应中，上皮存在时也受到抑制。上皮的作用并非由抑制性前列腺素或一氧化氮合酶产物的产生所致。此外，上皮并非乙酰胆碱降解的代谢位点。中性内肽酶抑制剂磷酰胺素模拟了去除上皮对高频刺激的胆碱能反应以及对乙酰胆碱诱导效应的影响。中性内肽酶抑制并未进一步增强去上皮段的反应。因此，我们认为上皮的抑制功能部分可由中性内肽酶的活性来解释，它限制了速激肽对胆碱能反应的兴奋作用。炎症反应和上皮损伤导致的中性内肽酶活性改变可能有助于哮喘气道高反应性的发生机制。
